The highly innovative “triple therapy” conducted by research scientists at the University of Texas Health Science Center at San Antonio for the management of serum blood glucose levels in Diabetics is receiving critical acclaim. The novel approach entails a new strategy to manage recently diagnosed, treatment-naive, Type 2 diabetes.
Researchers suggested that initiation of simultaneous administration of a 3-drug regimen that includes pioglitazone, glucagonlike peptide-1 (GLP-1), and agonist exenatide along with metformin — “Triple therapy” –is a fairly helpful approach in controlling the HbA1c levels (with lesser risk of hypoglycemic episodes and weight gain associated with abnormal metabolism in diabetics). This approach is supposedly better than the conventional approach to treat diabetes that involve step –wise delivery of metformin followed by sulfonylurea (glyburide), and basal insulin (glargine).
The results of this new study have been released at American Diabetes Association (ADA) 2013 Scientific Sessions.
University of Texas Health Science Center researcher, Dr. Muhammad A. Abdul-Ghani, presented the findings. He commented in a briefing:
“We think this might be clinically meaningful and, hopefully, in a larger study, it might show differences in the risk of microvascular complications, and that definitely will be [practice] changing, in terms of guidelines and the approach to treating patients.”
Dr. Abdul-Ghani suggested that the conventional step-wise approach affects the serum blood sugar control that is marked by fluctuating HbA1C concentration. However, as part of this study, the patients who were maintained on the triple regimen presented same concentration of HbA1C at 6 month and 2- year clinical assessment. Dr. Ghani further added that the study is ongoing and at the completion of approximately 3 years of study, the results have been consistent so far. He suggested: “So far, there is no other therapy that has shown such a durable and stable reduction in HbA1c.”
Details of the study:
The data presented by Dr. Abdul-Ghani reflected the data collected from 155 newly diagnosed and drug-naïve patients. The patients had an average of HbA1C concentration of 8.6% (demographic data suggests mean age of 46 and BMI of 36-37) in study participants.
Triple therapy group:
All the patients in this group were started on 3-drug regimen (15 mg/day of pioglitazone, 1000 mg/day of metformin and 5 µg twice daily of exenatide). The study permitted the increments in the dose to about 30 mg, 2000 mg, and 10 µg, respectively for each agent, by the end of month 1.
Diabetics who were randomly assigned to conventional drug regimen were advised metformin in a dose of 1000 mg/day in month 1 that was increased to a maximum of 2000 mg/day. Glyburide in a dose of 5 mg/day was added to the regimen if a rise of 100 mg/dL was noticed in the fasting plasma glucose (FPG)
The dose of Glyburide was doubled to 10 mg/day with FPG exceeding 100 mg/dL or HbA1c higher than 6.5% in month 2. Glargine insulin (10 U/day) was initiated in month 3 with FPG concentration of 100 mg/dL or HbA1c higher than 6.5%. A 10 units/day increase in the glargine dose was advised in patients who had higher FPG concentration (above 100 mg/dL) despite these measures.
Patients were evaluated in the clinical setting at every 3-month interval, and their response to medications was evaluated by tests like FPG, HbA1c, weight, and home blood glucose. Dose adjustment was performed in patients who had symptoms of hypoglycemia or blood glucose less than 60 mg/.
Potential benefits and side effects of Triple therapy:
At the end of two- years, following benefits were observed in the two study groups.
- Mean HbA1c of 6.0% in patients who were maintained on Triple therapy compared to a higher HbA1c of 6.6% in patients who were maintained on conventional hypoglycemic treatment.
- By the end of 2 years, almost 60% patients on Triple therapy reported HbA1c of less than 6.0% as opposed to only 27% in the control group. In addition, 92% had HbA1c less under 7mg/dL as opposed to only 72% in the control group.
- A weight loss of about 1.2 kg on Triple therapy group as opposed to weight gain in control group.
Besides these major findings, more treatment failure cases (42%) and hypoglycemic episodes (46%) were reported in the conventional therapy group as compared to triple therapy (17% and 15% respectively).
However, the incidence of gastrointestinal side effects in triple therapy was reportedly higher as compared to conventional therapy.
The following video provides an overview of Type 2 diabetes:
Dr Abdul Ghani commented:
“We were able to normalize the HbA1c in 60% of the people [on triple therapy], without much hypoglycemia, which we know has a very big adverse effect. We actually have weight loss, on average [in the triple-therapy group], despite having a maximal or near-maximal dose of pioglitazone, because of the combination with the GLP-1 [agonist], which mitigates the weight gain. That doesn’t mean that every patient lost weight, but on average we have a decrease.”
Comments and Applause from other researchers:
Researchers from all over the America and other parts of the world are very excited about the study, and are anxiously waiting for results that future years have to offer.
Professor of Medicine, Dr. Carol Wysham from University of Washington, School of Medicine suggested:
“I’m very excited by this, by any concept that will help to spare beta cells and that has extreme durability and will keep patients stable for longer.”
However, she also suggested that a lot of future research work is needed in order to implement this practice and definitely the results will take a lot of time to produce a noticeable inference; she said:
“First of all, you can’t take any single study of 100 patients and extrapolate that. I think it’s going to be like anything else in medicine: it’s going to be 10 years before it does get into common practice.”
University of North Carolina researcher Dr. John Buse suggested that although the approach to the therapy is fair and it is beyond doubt that the 3- drug therapy is far more effective and consistent at producing results. However, he also suggested that the control arm did well too. He also suggested that a better use of comparator drugs could have improved the credibility approach of the study
Canadian professor Lawrence A. Leiter from departments of medicine and nutritional sciences at the University of Toronto, Ontario gave his remarks in these words:
“These are very provocative results. The fact that they were able to achieve a mean HbA1c of 6%, which was sustained over the duration of the trial, was very impressive. I think one might quibble with the comparators that were used, but nonetheless it certainly is a paradigm shift.”
The study is ongoing and hopefully if the results remain consistent, triple therapy may replace conventional hypoglycemic therapy in near future.